Large collections (libraries) of organic molecules have emerged as important tools for the successful identification of useful compounds. Such libraries have typically been synthesized using combinatorial approaches (see, e.g., Gallop, et al., 1994; Gordon, E. M., et al., 1994). Several different methods have been used to assemble combinatorial libraries of various compounds. One such methodology was disclosed in Geysen, et al. Geysen's method involves functionalizing the termini of polymeric rods and sequentially immersing the termini in solutions of individual amino acids. A second method of peptide or oligonucleotide synthesis was developed by Affymax Technologies N.V. and disclosed in U.S. Pat. No. 5,143,854. The Affymax method involves sequentially using light for illuminating a plurality of polymer sequences on a substrate and delivering reaction fluids to said substrate. This method of synthesis produces large numbers, but relatively small quantities of products. A further method and device for producing peptides or oligonucleotides is disclosed in Houghton, E.P.O. 196174. Houghton's apparatus is a polypropylene mesh container or sac, similar to a tea-bag, which encloses reactive particles.
While combinatorial chemistry synthetic schemes such as the methods described above can generate large numbers of different compounds with a minimum number of steps, they have certain disadvantages. As mentioned above, some of the methods are capable of producing only limited quantities of each compound. Furthermore, the compounds are often synthesized and screened in "pools" or "batches". This can result in loss of potentially valuable information during screening if, for example, a particular pool contains compounds which possess both agonist and antagonist activities. Further, once a pool is identified as containing a potentially active compound, the identity of the active compound must be determined. This identification or decoding requires some type of deconvolution or tagging protocol, requiring additional steps to identify the active compound.
Parallel synthesis strategies do not suffer from the above-mentioned disadvantages of combinatorial approaches, as a single compound is generated and assayed (see, e.g., Sugarman, et al., U.S. Pat. No. 5,503,805, issued Apr. 2, 1996). The disadvantage of parallel synthesis strategies is that presently-available instrumentation for carrying out such syntheses is costly and complex, requiring large number of valves, separate pieces of tubing, and the like. Accordingly, it is generally not suitable for the synthesis of large numbers (e.g., &gt;100) of compounds. Currently available parallel synthesis instruments are typically limited in their capacity to between 12 and 24 reaction vessels for automated instruments and 96 reaction vessels for manual instruments.
Thus, there is a need for simple and efficient systems and methods for synthesizing large numbers of compounds, that do not suffer from the above disadvantages of combinatorial approaches or the complexity and limitations of currently-available parallel synthetic approaches. The present invention provides such systems and methods.